High-performance Mass Spectrometry Research Articles

Characterization of CGK012 in rat plasma by high performance liquid chromatography and mass spectrometry (HPLC–MS/MS): Application to a pharmacokinetic study

CGK012 is a newly synthesized pyranocoumarin substance suppressing the activation and transcription of β-catenin related to Wnt3a-CM. A bioanalytical method for CGK012 was developed and validated in rat plasma, and the method was applied to determine the plasma concentrations after intravenous administration. Plasma was cleaned-up by protein precipitation by acetonitrile including an internal standard. The substances were separated on a reversed-phase column, and the mobile phase was a mixture of water and acetonitrile (3:7, v/v; 0.1 % formic acid). The mass transition occurred at m/z 358.2→229.2 for CGK012 [M+H]+. CGK012 was stable in the various conditions, and the present assay met the criteria of bioanalytical method validation. CGK012 bi-exponentially decayed with the half-life of 4.0 h at the terminal phase. Mean Vd and clearance were 0.69 L/kg and 1.31 L/h/kg, respectively. This is the first bioanalytical method developed for quantification of CGK012 in rat plasma using LC–MS/MS, which would be useful to examine pharmacokinetic study of the substance.

Identification of Functional Interactome of Gastric Cancer Cells with Helicobacter pylori Outer Membrane Protein HpaA by HPLC-MS/MS.

HpaA as an outer membrane protein of Helicobacter pylori (H. pylori) plays a significant role in the adhesion to the human stomach, but the functional relation between HpaA and gastric epithelial cells is still not clear. To screen the interaction between HpaA and cellular proteins in gastric epithelial cells, the HpaA protein from H. pylori 26695 fused with a tag (6× His) was expressed and purified successfully, the secondary structure was estimated by the Circular Dichroism (CD) spectrum, and the purified recombinant protein was used to perform the pull-down assays with gastric cancer cell lines (AGS and SGC-7901) lysates, respectively. The pull-down proteins were identified by high-performance liquid chromatography tandem mass spectrometry system (HPLC-MS/MS). A total of 9 and 13 proteins related were analyzed from AGS and SGC-7901 cell lysates, respectively. ANXA2 was considered as putative HpaA functional partner discovered from lysates of both cell lines with high score and coverage. It is hypothesized that HpaA may be involved in the biological process of regulation of transcription and nucleic acid metabolism during the adhesion of H. pylori to human gastric epithelial cells, and HpaA-binding proteins also be used as targets for the development of antiadhesion drugs against H. pylori.

RETRACTED ARTICLE: Light hydrocarbon geochemistry: insight into oils/condensates families and inferred source rocks of the Woodford\u2013Mississippian tight oil play in North-Central Oklahoma, USA

The Woodford–Mississippian “Commingled Production” is a prolific unconventional hydrocarbon play in Oklahoma, USA. The tight reservoirs feature variations in produced fluid chemistry usually explained by different possible source rocks. Such chemical variations are regularly obtained from bulk, molecular, and isotopic characteristics. In this study, we present a new geochemical investigation of gasoline range hydrocarbons, biomarkers, and diamondoids in oils from Mississippian carbonate and Woodford Shale. A set of oil/condensate samples were examined using high-performance gas chromatography and mass spectrometry. The result of the condensates from the Anadarko Basin shows a distinct geochemical fingerprint reflected in light hydrocarbon characterized by heptane star diagrams, convinced by biomarker characteristics and diamantane isomeric distributions. Two possible source rocks were identified, the Woodford Shale and Mississippian mudrocks, with a variable degree of mixing. Thermal maturity based on light hydrocarbon parameters indicates that condensates from the Anadarko Basin are of the highest maturity, followed by “Old” Woodford-sourced oils and central Oklahoma tight oils. These geochemical parameters shed light on petroleum migration within Devonian–Mississippian petroleum systems and mitigate geological risk in exploring and developing petroleum reservoirs.

A Pilot Comparative Pharmacokinetic Study on Mango Polyphenols After Acute Intake of Fresh and Individual Quick Frozen Mango Pulp in Healthy Human Subjects

Abstract Objectives The objective of this study was to characterize and compare the pharmacokinetic profile of polyphenolic metabolites after acute intake of fresh and individually quick frozen (IQF) mango pulp in human plasma over 24 hours. Methods Healthy human subjects (n = 7, age = 31 ± 3 years, BMI = 22.7 ± 0.6 kg/m2) received IQF or fresh mango pulp (500 g) or control (100 mg vitamin C) in random order after 3-day low polyphenol diet in a cross over study design. Polyphenols in mango pulps (fresh and IQF) and their metabolites were characterized in plasma collected before (fasting, baseline) and at 30 min or hourly intervals for 8 h then again at 24 h using ultra high performance liquid chromatography and mass spectrometry (UHPLC-MS). Multiple comparisons within and among treatments (IQF and Fresh) over 24 h postprandial time were performed by mixed model using SAS with statistical significance set at P < 0.05. Results Gallic acid (228.1 ± 7.3 µg/100 g fresh weight, FW) and galloyl glucose (5.0 ± 0.2 µg/100 FW) were significantly higher (P < 0.05) in fresh compared to IQF mango pulp. In plasma however, gallic acid (Cmax = 17.3 ± 4.0 nmol/L, AUC0–24h = 63.9 ± 7.9 nmol × h/L), galloyl glucose (Cmax = 12.4 ± 2.3 nmol/L, AUC0–24h = 49.2 ± 8.1 nmol × h/L), ferulic acid hexoside (Cmax = 2.8 ± 0.5 nmol/L, AUC0–24h = 8.6 ± 1.9 nmol × h/L), and gallic acid and pyrogallol metabolites (sulfates, methyl and glucuronides) were significantly higher after IQF mango pulp intake compared to fresh mango pulp as assessed by maximum concentrations achieved (Cmax) and area under the curve (AUC0–24 h). Conclusions These results indicate that IQF may preserve or enhance the bio-accessibility of mango (poly)phenol components compared to fresh mangoes, which are hot water treated before importing into the USA. Funding Sources This study was funded by the National Mango Board.

Electrodes based on zeolites modified with cobalt and/or molybdenum for pesticide degradation: part II—2,4,6-trichlorophenol degradation

2,4,6-trichlorophenol (TCP) is a persistent pollutant introduced in water by industrial processes and pesticides. We have studied the electrooxidation of TCP on glassy carbon (GC) electrodes drop-coated with a suspension containing Mo- and/or Co-modified zeolite, graphite, and Nafion® perfluorinated ion-exchange resin in distilled water. Three zeolites, Linde type A (ZA), Faujasite (ZY) and MFI (ZSM-5), of different hydrophilic/hydrophobic character, were modified with molybdenum and/or cobalt by the wet impregnation method and characterized by Fourier-transform infrared spectroscopy with attenuated total reflection and temperature programmed reduction. The electrochemical study included cyclic voltammetry, electrochemical impedance spectroscopy, and electrolysis at controlled potential. High performance liquid chromatography and mass spectrometry allowed detecting the following reaction products: 2,6-dichloro-1,4-benzoquinone, 2,6-dichloro-1,4-hydroquinone, 3,5-dichloro-2-hydroxy-1,4-benzoquinone, and malic, maleic, picric, and acetic acids. A maximum degradation of about 90% was reached after 4 h of electrolysis at 0.83 V vs Ag/AgCl/KCl 3 M, using a GC/graphite-ZSM5Mo electrode. The electrodes modified with Mo, and especially that with ZSM5, the most hydrophobic zeolite, were active for the degradation of TCP. We conclude that the main role of the Mo species is to catalyze the hydrogen peroxide decomposition yielding reactive singlet oxygen, as evidenced by the pink color of 3,5-dichloro-2-hydroxy-1,4-benzoquinoneand confirmed by mass spectrometry.

The association between IDO activity and clinical prognosis in patients with early stage non-small cell lung cancer after stereotactic body radiotherapy.

e21054 Background: Immunity affects the efficacy of radiotherapy of lung cancer patients. Indoleamine 2,3-dioxygenase (IDO) is a key enzyme that converts tryptophan (T) into heparin (K), which can promote immune suppression and assist tumor cells in immune evasion. The purpose of this study was to quantitatively analyze the immune activity of IDO in serum before and after SBRT, and to explore the changes in immune activity of IDO mediated by SBRT and its relationship with patient's survival. Methods: High-performance liquid chromatography and mass spectrometry were used to determine serum K and T in 30 patients with early non-small cell lung cancer before and after SBRT treatment. K: T stands for IDO activity. The Kaplan-Meier method and log-rank test were used to evaluate the correlation between overall survival (OS), progression-free survival (PFS), and IDO activity. Cox proportional hazards model was used for univariate and multivariate analyses. Results: The median follow-up time was 37.4 months. The median PFS was 37.5 (95% CI, 31.0-44.0) months. The median survival was not reached. In all patients, lower post/pre kynurenine ratio correlated significantly with better PFS (HR = 0.31, 95% CI = 0.11-0.90, P = 0.032). The lower K: T ratio at post-RT received longer OS (HR = 0.27, 95% CI = 0.079-0.95, P = 0.042). In multivariate analysis, smoking < 30 packs / year (P = 0.030), higher BED (P < 0.001), and lower post/pre kynurenine (P = 0.043) were associated with better PFS. Lower K: T ratio post-RT (P = 0.040) and higher BED (P < 0.001) were significantly associated with better OS. Conclusions: SBRT could alter IDO-mediated antitumor immune activity. The lower level of post/pre kynurenine ratio was significantly related with better PFS. The lower K: T ratio at post-RT was related with better OS. This study shows that IDO is a potentially valuable biomarker for monitoring the immune status and predicting survival in early NSCLC patients after SBRT.

Plasma-Derived Extracellular Vesicle Phosphoproteomics through Chemical Affinity Purification.

The invasive nature and the pain caused to patients inhibit the routine use of tissue biopsy-based procedures for cancer diagnosis and surveillance. The analysis of extracellular vesicles (EVs) from biofluids has recently gained significant traction in the liquid biopsy field. EVs offer an essential "snapshot" of their precursor cells in real time and contain an information-rich collection of nucleic acids, proteins, lipids, and so on. The analysis of protein phosphorylation, as a direct marker of cellular signaling and disease progression could be an important stepping stone to successful liquid biopsy applications. Here we introduce a rapid EV isolation method based on chemical affinity called EVtrap (extracellular vesicle total recovery and purification) for the EV phosphoproteomics analysis of human plasma. By incorporating EVtrap with high-performance mass spectrometry (MS), we were able to identify over 16 000 unique peptides representing 2238 unique EV proteins from just 5 μL of plasma sample, including most known EV markers, with substantially higher recovery levels compared with ultracentrifugation. Most importantly, more than 5500 unique phosphopeptides representing almost 1600 phosphoproteins in EVs were identified using only 1 mL of plasma. Finally, we carried out a quantitative EV phosphoproteomics analysis of plasma samples from patients diagnosed with chronic kidney disease or kidney cancer, identifying dozens of phosphoproteins capable of distinguishing disease states from healthy controls. The study demonstrates the potential feasibility of our robust analytical pipeline for cancer signaling monitoring by tracking plasma EV phosphorylation.

Introduction of the Menaquinone Biosynthetic Pathway into Rhodobacter sphaeroides and de Novo Synthesis of Menaquinone for Incorporation into Heterologously Expressed Integral Membrane Proteins.

Quinones are redox-active molecules that transport electrons and protons in organelles and cell membranes during respiration and photosynthesis. In addition to the fundamental importance of these processes in supporting life, there has been considerable interest in exploiting their mechanisms for diverse applications ranging from medical advances to innovative biotechnologies. Such applications include novel treatments to target pathogenic bacterial infections and fabricating biohybrid solar cells as an alternative renewable energy source. Ubiquinone (UQ) is the predominant charge-transfer mediator in both respiration and photosynthesis. Other quinones, such as menaquinone (MK), are additional or alternative redox mediators, for example in bacterial photosynthesis of species such as Thermochromatium tepidum and Chloroflexus aurantiacus. Rhodobacter sphaeroides has been used extensively to study electron transfer processes, and recently as a platform to produce integral membrane proteins from other species. To expand the diversity of redox mediators in R. sphaeroides, nine Escherichia coli genes encoding the synthesis of MK from chorismate and polyprenyl diphosphate were assembled into a synthetic operon in a newly designed expression plasmid. We show that the menFDHBCE, menI, menA, and ubiE genes are sufficient for MK synthesis when expressed in R. sphaeroides cells, on the basis of high performance liquid chromatography and mass spectrometry. The T. tepidum and C. aurantiacus photosynthetic reaction centers produced in R. sphaeroides were found to contain MK. We also measured in vitro charge recombination kinetics of the T. tepidum reaction center to demonstrate that the MK is redox-active and incorporated into the QA pocket of this heterologously expressed reaction center.

Diketopiperazines and other bioactive compounds from bacterial symbionts of marine sponges.

Humanity faces great challenges, such as the rise of bacterial antibiotic resistance and cancer incidence. Thus, the discovery of novel therapeutics from underexplored environments, such as marine habitats, is fundamental. In this study, twelve strains from the phylum Firmicutes and thirty-four strains from the phylum Proteobacteria, isolated from marine sponges of the Erylus genus, collected in Portuguese waters, were tested for bioactivities and the secondary metabolites were characterised. Bioactivity screenings comprised antimicrobial, anti-fungal, anti-parasitic and anti-cancer assays. Selected bioactive extracts were further analysed for already described molecules through high performance liquid chromatography and mass spectrometry. Several bioactivities were observed against the fungus Aspergillusfumigatus, the bacteria (methicillin-resistant Staphylococcus aureus and Escherichia coli), the human liver cancer cell line HepG2 and the parasite Trypanosoma cruzi. Medium scale-up volume extracts confirmed anti-fungal activity by strains Proteus mirabilis #118_13 and Proteus sp. (JX006497) strain #118_20. Anti-parasitic activity was also confirmed in Enterococcus faecalis strain #118_3. Moreover, P. mirabilis #118_13 showed bioactivity in human melanoma cell line A2058 and the human hepatocellular carcinoma cell line HepG2. The dereplication of bioactive extracts showed the existence of a variety of secondary metabolites, with some unidentifiable molecules. This work shows that bacterial communities of sponges are indeed good candidates for drug discovery and, as far as we know, we describe anti-parasitic activity of a strain of E. faecalis and the presence of diketopiperazines in Proteus genus for the first time.

Targeted Metabolomic Profiling Reveals Association Between Altered Amino Acids and Poor Functional Recovery After Stroke.

Amino acids have been shown to be among the most important metabolites to be altered following stroke; however, they are a double-edged sword with regard to regulating hemostasis. In this study, we conducted a targeted metabolomic study to examine the association between serum levels of amino acids and functional recovery after stroke. Three hundred and fifty-one patients with stroke admitted to an acute rehabilitation hospital were screened, and 106 patients were selected based on inclusion and exclusion criteria. Recruited patients were stratified using Montebello Rehabilitation Factor Score (MRFS) efficiency. We selected the top (n = 20, 19%) and bottom (n = 20, 19%) of MRFS efficiency for metabolomic analysis. A total of 21 serum amino acids levels were measured using ultra high performance liquid chromatography and mass spectrometry. The normalized data were analyzed by multivariate approaches, and the selected potential biomarkers were combined in different combinations for prediction of stroke functional recovery. The results demonstrated that there were significant differences in leucine-isoleucine, proline, threonine, glutamic acid, and arginine levels between good and poor recovery groups. In the training (0.952) and test (0.835) sets, metabolite biomarker panels composed of proline, glutamic acid, and arginine had the highest sensitivity and specificity in distinguishing good recovery from poor. In particular, arginine was present in the top 10 combinations of the average area under the receiver operating characteristic curve (AUC) test set. Our findings suggest that amino acids related to energy metabolism and excitotoxicity may play an important role in functional recovery after stroke. Therefore, the level of serum arginine has predictive value for the recovery rate after stroke.

Speciation of thioarsenicals through application of coffee ring effect on gold nanofilm and surface-enhanced Raman spectroscopy

Thioarsenicals, such as dimethylmonothioarsinic acid (DMMTAV) and dimethyldithioarsinic acid (DMDTAV), have been increasingly discovered as important arsenic metabolites, yet analysis of these unstable arsenic species remains a challenging task. A method based on surface-enhanced Raman spectroscopy (SERS) detection in combination with the coffee ringeffect for separation is expected to be particularly useful for analysis of thioarsenicals, thanks to minimal sample pretreatment and unique fingerprint Raman identification. Such a method would offer an alternative approach that overcomes limitations of conventional arsenic speciation techniques based on high performance liquid chromatography separation and mass spectrometry detection. A novel analytical method based on combination of the coffee ringeffect and SERS was developed for the speciation of thiolated arsenicals. A gold nanofilm (AuNF) was employed not only as a SERS substrate, but also as a platform for the separation of thioarsenicals. Once a drop of the thioarsenicals solution was placed onto the AuNF and evaporation of the solvent and the ring stamp formation onto AuNF began, the SERS signal intensity substantially increased from center to edge regions of the evaporated droplet due to the presence of the coffee ring effect. Through calculating the pKa’s of DMMTAV and DMDTAV and accordingly manipulating the chemical environment, separation of these thioarsenicals was realized as they travelled different distances during the development of the coffee ring. The migration distances of individual species were influenced by a radial outward flow of a solute, the thioarsenicals-AuNF interactions and a thermally induced Marangoni flow. The separation of DMMTAV (center) and DMDTAV (edge) on the coffee ring, in combination with fingerprint SERS spectra, enables the identification of these thioarsenicals by this AuNF-based coffee ring effect-SERS method.

Water Hyacinth Control by Glyphosate Herbicide and Its Impact on Water Quality

The aim of this study was to evaluate the herbicide glyphosate under aquatic environment conditions, in a controlled and closed experimental field, in the management of water hyacinth (Eichhornia crassipes) in reservoirs. Twenty reservoirs (polyethylene water tanks) with storage capacity of 1000 liters were used, without water flow and without evapotranspired water replacement (worst case), being 04 for each treatment. The adult plants were placed in the water tanks to provide 90% surface occupation of the reservoir. Five treatments with four repetitions were considered, being: 1) Reservoir colonized by water hyacinth without control; 2) Reservoir colonized by water hyacinth, controlled by glyphosate; 3) Reservoir colonized by water hyacinth, controlled by freezing; 4) Reservoir without water hyacinth and glyphosate application and 5) Reservoir without water hyacinth and no glyphosate application. The glyphosate herbicide was used at the highest recommended dose, 7.0 L·ha-1 or 3360 g of acid equivalent per ha, applied using carbon dioxide precision equipment (backpack sprayer), providing a flow rate of 200 L·ha-1. The water samples were collected at the time of application, 6, 12, 18 and 24 hours after application and also at 2, 4, 8, 16, 32 and 64 days after application, in the morning, always at the same time, also between 8 and 9 h. The method used for determination of residues was by high performance liquid chromatography (HPLC) and mass spectrometry with a mass selective detector. Low concentrations of glyphosate and aminomethylphosphonic acid (AMPA) were found in both reservoirs that received application of the product. The half-life of glyphosate in water to the reservoirs with water hyacinth was 11 days and in the reservoirs without water hyacinth was 21 days. The results show a low potential of environmental impact of glyphosate use in the control of water hyacinth in reservoirs.

Identification and photolytic characteristics of benzoquinone intermediates in photo Fenton system

ABSTRACT The predecessors believed that the rufous intermediates of benzene compounds degradation was quinhydrone. This article corrects this misperception. This paper takes benzene, phenol, chlorobenzene and nitrobenzene as the substrates, and p-benzoquinone as the reference; we studied the degradation law of benzene compounds in Fenton system. During the process of benzene, phenol, chlorobenzene and nitrobenzene degradation by Fenton method, it is found that the use of hydroxyl radical system for visible light would be enhanced as soon as the rufous substances were produced, which indicated that rufous substances have elevated photosensitivity. The analyses via high performance liquid chromatography, mass spectrometry, infrared spectroscopy and UV–visible spectroscopy indicate the common rufous substance is a kind of polymer formed by p-benzoquinone and oxygen. The yield of photoinduced electrons, singlet oxygen and superoxide anion radicals are carried to higher level by the rufous substance. The outstanding photosensitivity of the rufous substance provides a new idea for the treatment of wastewater containing benzene compounds by visible light.

Soil metaproteomics as a tool for monitoring functional microbial communities: promises and challenges

Soil is a complex and dynamic network of different biological processes linked in an intricate manner to facilitate effective ecosystem functioning. Microbial diversity and its functioning are crucial to effective ecosystem working and its sustenance. Metagenomic studies undertaken to-date have illustrated the tremendous diversity of both culturable and unculturable microbiome in specific ecosystems, but their exact role in ecosystem functioning needs to be addressed. This can be undertaken by studying the protein repertoire in the ecosystem, which are the direct and undeviating key players in the ongoing metabolic processes. Metaproteomics, an emerging science, tries to snapshot the entire proteins present in a specific environment at a particular time interval. It links the phylogeny and functionality of soil microorganisms, describing not only at the level of the individual dominant organism, but also at the community level, therefore, profiling microbial enzymes may be a sensitive indicator of the soil ecosystem. With the emergence of high-performance mass spectrometry, the approach to mine these functional complex soil microbiomes became feasible; however, it is hindered by the presence of innumerable interfering molecules present in the soil samples. This review focuses on recent developments in soil metaproteomics, particularly, in terms of protein extraction methodologies and mass spectrometry-based measurements, as well as their applications in soil based approaches to decipher the underlying processes responsible for differential functioning in diverse environments.

Evaluation of Ultra-High-Performance Liquid Chromatography (HPLC) Tandem Mass Spectrometry for Determination of Avermectin Residues in Milk

The study was conducted to evaluate the applicability of ultra high-performance liquid chromatography - tandem mass spectrometry method (UHPLC-MS/MS), establish the MS/MS detection parameters and determine the validation characteristics for the analysis of residual content of avermectins in milk. The UHPLC-MS/MS method has proved to be accurate, practical and universal. This was confirmed by Decision limit (CCα) data: abamectin - 12.56 μg/kg, doramectin - 17.74 μg/kg, eprinomectin - 24.02 μg/kg, ivermectin - 12.53 μg/kg, moxidectin - 44.69 μg/kg, recovery is 88.7-110%. The data obtained for assessing the suitability, accuracy and reproducibility of the results meet the requirements of the European Directive (2002/657/EC). The efficient ultra high-performance liquid chromatography tandem mass spectrometry (UHPLC-MS/MS) method that was developed and adopted for routine use by the laboratories of veterinary medicine, allows to detect residual quantities of 5 avermectins used in animal breeding for the prevention of helminthiases in food products including milk.

A Subcellular Quantitative Proteomic Analysis of Herpes Simplex Virus Type 1-Infected HEK 293T Cells.

Herpes simplex virus type 1 (HSV-1) is widespread double-stranded DNA (dsDNA) virus that establishes life-long latency and causes diverse severe symptoms. The mechanisms of HSV-1 infection and HSV-1’s interactions with various host cells have been studied and reviewed extensively. Type I interferons were secreted by host cells upon HSV infection and play a vital role in controlling virus proliferation. A few studies, however, have focused on HSV-1 infection without the presence of interferon (IFN) signaling. In this study, HEK 293T cells with low toll-like receptor (TLR) and stimulator of interferon genes protein (STING) expression were infected with HSV-1 and subjected to a quantitative proteomic analysis. By using a subcellular fractionation strategy and high-performance mass spectrometry, a total of 6607 host proteins were quantified, of which 498 proteins were differentially regulated. A bioinformatics analysis indicated that multiple signaling pathways might be involved in HSV-1 infection. A further functional study indicated the role of Interferon-induced transmembrane protein 3 (IFITM3), Coiled-coil-helix-coiled-coil-helix domain-containing protein 2 (CHCHD2), and Tripartite motif-containing protein 27 (TRIM27) in inhibiting viral DNA replication and proliferation. Our data provide a global view of host responses to HSV-1 infection in HEK 293T cells and identify the proteins involved in the HSV-1 infection process.

Development of a method for preparing octreotide derivative for diagnosis of neuroendocrine tumors

Currently the development of technologies for labeling somatostatin with technetium-99m for diagnosing radionuclide neuroendocrine tumors is under way. Somatostatin analogues are binded with technetium99m only by the preliminary addition of a chelating agent. Therefore, it is important to develop a method for preparation of an octreotide derivative by modifying octreotide with precursors: ligands with high chelating ability for its tight binding with technetium-99m. ω-Bis(pyridin-2-ylmethyl)amino)aliphatic acids can be used successfully as such precursors.The purpose of the study was to develop a method for obtaining a new octreotide derivative for diagnosing neuroendocrine tumors.Materials and methods. The somatostatin octreotide analogue was used as the object of the study; succinimid-1-yl 6-(bis(pyridin-2-ylmethyl)amino)hexanoate was used as a chelating agent. Methods of high performance liquid chromatography and mass spectrometry were used to separate and analyze the synthesized compounds.Results. A method to produce an original octreotide derivative using a succinimid-1-yl 6-(bis(pyridin2-ylmethyl)amino)hexanoate as a chelating agent was proposed. The conditions of analytical and semipreparative HPLC for the analysis and purification of the active octreotide derivative (a monosubstituted derivative of the amino acid residue of D-phenylalanine) were suggested.Conclusion. The synthesized derivative of octreotide has a chelating center for strong binding to technetium-99m in its structure, which can be useful for diagnosing neuroendocrine tumors.

Determinación y comparación cualitativa de cannabinoides presentes en productos naturales comerciales del departamento del Cauca-Colombia

Actualmente, hay un creciente interés por el estudio de Cannabis sativa y sus componentes ya que se le atribuye propiedades terapéuticas en el tratamiento de enfermedades. En Colombia y específicamente en el departamento del Cauca se comercializan productos de cannabis tanto para fines no medicinales como terapéuticos. En consecuencia, es necesario el análisis de estos productos de manera que se pueda conocer la composición de los mismos y el posible efecto que pueda tener sobre la salud.El análisis de los componentes de estos productos se llevó a cabo empleando la cromatografía líquida de alta resolución (CLAR) y espectrometría de masas (EM), de tal manera que permitieron la identificación de las principales especies cannabinoides; Δ9tetrahidrocannabinol (THC), cannabidiol (CBD), cannabinol (CBN), cannabigerol (CBG). La separación de los analitos se llevó a cabo mediante la implementación de una columna analítica C18 de fase reversa, elución isocrática 1 mL/min, presión del sistema 800 PSI, una mezcla de acetonitrilo ACN y buffer fosfato (KHPO4) en relación 65/35 como fase móvil, volumen de inyección de 10 µL, un tiempo de análisis de 15 min, y detección a 220 nm.

Sphenopalatine Ganglion Stimulation Upregulates Transport of Intra-Arterial Temozolomide Across the Blood-Brain Barrier

Abstract INTRODUCTION Sphenopalatine ganglion (SPG) stimulation has been shown to reversibly alter blood–brain barrier (BBB) permeability. At the present time, it is widely used for the treatment of cluster headaches in Europe and is well tolerated for this use in humans. METHODS In a rat model, we assessed the permeability of intra-arterial temozolomide with and without sphenopalatine ganglion stimulation. We developed a high-performance liquid chromatography and mass spectrometry method to measure temozolomide in rat plasma and brain tissue, with caffeine as the internal standard. RESULTS Here we show a statistically significant (P = .0006), 5-fold upregulation of TMZ crossing the BBB and reaching brain parenchyma in rats receiving low-frequency (LF, 10 Hz) SPG stimulation. CONCLUSION Glioblastoma multiforme (GBM) remains an extremely difficult disease to treat. Since 2004, the gold standard of treatment for GBM in the United States includes surgery + TMZ and radiation. Our treatment paradigm shows a mechanism in which we could more effectively and safely deliver TMZ in a targeted manner, to minimize systemic toxicity and maximize action at the target tissue. The SPG Stimulation treatment paradigm could be used in a broad spectrum of central nervous system (CNS) pathologies.

The BiOCl/diatomite composites for rapid photocatalytic degradation of ciprofloxacin: Efficiency, toxicity evaluation, mechanisms and pathways

The activity and separation performance of nano-structure photocatalyst have always been the focus in the field of environmental pollutant removal. In this work, BiOCl/diatomite composites were successfully fabricated via a simple hydrolysis method, which could meet the above two requirements. The superior performance of composites was explained by using X-ray diffractometer (XRD), Fourier transform infrared spectra (FTIR), scanning electron microscopy (SEM) and transmission electron microscopy (TEM). The results revealed that the tetragonal phase BiOCl and diatomite coexisted in the composites, producing the synergistic effect. The diatomite had the high adsorption and silicon hydroxyl groups while the BiOCl had the exposed (001) facets. Diatomite as a carrier was actually equivalent to a solid dispersant, which could immobilize BiOCl microspheres evenly on its surface and prevent their aggregation, guaranteeing more active sites of BiOCl be exposed and promoting the transfer and separation of photo-induced carriers. The prepared BiOCl/60%D presented 94% removal efficiency for ciprofloxacin (CIP) under simulated solar light within 10 min irradiation, and also presented a 42.9% of total organic carbon (TOC) removal after 240 min. Despite the mineralization of CIP was incomplete, toxicity assessment indicated effective elimination of CIP antibacterial property by BiOCl/60%D in a short time. Moreover, the BiOCl/60%D exhibited good stability and reusability. The formation mechanism of BiOCl/diatomite composites was speculated, meanwhile, the photocatalytic degradation mechanism and pathways of CIP were also deduced by using radicals trapping experiments, electron spin resonance (ESR), high performance liquid chromatography (HPLC) and mass spectrometry (MS). This study provided a simple method of building efficient BiOCl/diatomite composites for fast degradation of CIP in water, which had substantial attraction for application.